Process for the preparation of quinolines

ABSTRACT

In a process for treating 2-(beta-cyanoethyl)-cyclohexanones with a dehydrogenation catalyst to produce the corresponding quinolines, the improvement comprising passing the 2-(beta-cyanoethyl)-cyclohexanone over a dehydrogenation catalyst at temperatures below 230 DEG  C. and thereafter contacting the resulting reaction product, in the gaseous state and in the presence of hydrogen, at a temperature of over 230 DEG  C.

This is a continuation of application 532,294 filed Dec. 12, 1974, nowU.S. Pat. No. 4,028,362.

The invention relates to a process for preparing a reaction mixturecontaining quinoline, and alkyl substituted quinolines, in which a2-(beta-cyanoethyl)-cyclohexanone, or a substituted2-beta-cyanoethyl-cyclohexanone, is brought into contact with adehydrogenation catalyst in the gaseous phase in the presence ofhydrogen.

A process for preparing quinolines is disclosed in British PatentSpecification No. 1,304,155. According to this patent specification, areaction mixture containing quinoline and hydroquinolines is obtainedfrom 2-(beta-cyanoethyl)-cyclohexanone at a temperature of 250° C. witha conversion of 100%. In this case the actual yield of quinoline andhydroquinolines is 96% of the theoretical yield. Such a conversion andyield are, practically, very desirable. It has been found, however, thatthe catalyst, in that prior art process will have to be reactivatedafter some time, e.g. 200-300 hours, because the conversion and yieldwill otherwise fall off considerably. Frequent activation of thecatalyst renders such a process less practical for commercial purposes.

A process has now been found in which the catalyst can be usedconsiderably longer without reduction in the conversion and yields ofthe basic process.

SUMMARY OF THE INVENTION

The process according to the invention is characterized in that thegaseous starting mixture of 2-(beta-cyanoethyl)-cyclohexanone, or2-(beta-cyanoethyl)-substituted cyclohexanones, is first brought intocontact with the catalyst at a temperature of below 230° C. and theresulting reaction product is subsequently brought into contact with thecatalyst in the gaseous state and in the presence of hydrogen at atemperature of over 230° C. By reaction products is meant quinolines, aswell as hydroquinolines.

DETAILED DESCRIPTION OF THE INVENTION

The invention is directed to a process for contacting2-(beta-cyanoethyl)-cyclohexanones with dehydrogenation catalysts toproduce the corresponding quinolines. The process in accordance with theinvention is a two-stage process comprising contacting a gaseousstarting mixture of a 2-(beta-cyanoethyl)-cyclohexanone, or2-(beta-cyanoethyl)-substituted-cyclohexan-1-ones, with adehydrogenation catalyst at temperatures below 230° C. and subsequentlytreating the resulting reaction product by contacting the resultingreaction product with the catalyst, in the gaseous state and in thepresence of hydrogen at temperatures over 230° C. By this two-stepheating process, the lifetime of the catalyst is lengthened, withoutconcommitant reduction in conversion yields.

The first stage of the process, which requires treating2-(beta-cyanoethyl)-cyclohexanones, at temperatures below 230° C., maybe conducted at temperatures of 150° to 230° C. Preferably, thetemperature of the first stages of the process is conducted betweentemperatures of 185° to 220° C. The second stage of the process whichrequires contacting the products of the first stage of the process attemperatures above 230° C. may be conducted at temperatures between 230°and up to 400° C. Preferably, the temperature of the second stage of theprocess lies between 260° and 300° C. At preferred temperature ranges,the life of the dehydrogenation catalyst appears to be extremely long.

As set forth above, the gaseous starting material or reactant comprisesvaporized 2-(beta-cyanoethyl)-cyclohexanones. Also the process isapplicable to 2-(beta-cyanoethyl)-alkyl substituted cyclohexanones.Particularly, the reactants of the process are compounds of the generalformula ##STR1## wherein each of R₁, R₂, R₃, and R₄ is the same ordifferent, and is a hydrogen or an alkyl group of 1 to 4 carbon atoms.When alkyl substituted cyclohexanones are employed according to theprocess, the summation of the carbon atoms of R₁, R₂, R₃ and R₄ is nogreater than 10. According to one aspect of the invention, each of R₁,R₂, R₃ and R₄ is hydrogen. Generally, the cyclo-hexanone may contain oneor more alkyl groups in the 3, 4, 5 or 6 position of the cyclohexanonering. A process for preparing these starting materials is disclosed inU.S. Pat. No. 2,850,519, which is hereby incorporated by reference.

As stated above, the 2-(beta-cyanoethyl)-cyclohexanone is in the gaseousstate. The first stage of the process requires contacting the vaporized2-(beta-cyanoethyl)-cyclohexanone with the dehydrogenation catalyst.Optionally, the vaporized 2-(beta-cyanoethyl)-cyclohexanone may beadmixed with hydrogen gas for both steps of the process. In addition tohydrogen admixed with the gaseous starting material, the reactantmixture may contain nitrogen gas. The mole ratio of hydrogen toreactants may vary from 1,1 : 1 to 15 : 1. When nitrogen is present, themoles of hydrogen gas to moles of nitrogen gas may vary from 4 : 1 to 1: 1.

Various known dehydrogenation catalysts may be used in the process ofthe invention. The catalyst in the first and the second stages of theprocess of the invention may be the same or different. Normally thesecatalysts are used on a carrier, such as e.g., silica gel, aluminumoxide, magnesium oxide, and mixtures of these materials. For example,platinum on aluminum oxide may be used, nickel on silica gel, palladiumon aluminum oxide or copper on magnesium oxide. Examples of knownsuitable dehydrogenation catalysts, which may be used in the two-stageprocess of the invention, include metals or compounds of metals selectedfrom the class consisting of group VIII and group I B of the periodictable 5, such as copper, silver, gold, iron, nickel, cobalt, platinum,palladium, ruthenium, rhodium, osmium, and iridium. The catalyst may beused as a fixed bed, a fluid bed, or in any other way. The catalyst ofthe invention may be regenerated by known processes.

The space velocity in each stage of the process of the invention may bevaried, e.g. between 0.01 and 2 grams of starting cyanoketone permilliliter of catalyst mass per hour. The amount of hydrogen required inthe gaseous mixture, may vary, as set forth above. The amount is usuallyso chosen that after each stage at least 0.1 mole of hydrogen per moleof original cyanoketone is present as such. However, larger amounts ofhydrogen may be used without deleterious side effects. After terminationof the reaction, the hydrogen present may be recovered and recycled.

The gaseous reaction mixture obtained in the first stage of the processaccording to the invention will contain various amounts of water, as aby-product of the process. Preferably, this water will be separated off,since the second stage of the reaction process may be undertaken insmaller apparatus, although under otherwise similar conditions.

The reaction mixture obtained according to the process of the inventioncontains not only quinoline, or alternatively alkyl substitutedquinolines depending upon the 2-(beta-cyanoethyl)-cyclohexanone used,but also contains correspondingly unsubstituted or substitutedhydroquinolines. After condensation of the resulting gaseous reactionmixture, the mixture of quinolines and hydroquinolines may be separatedby distillation. If hydroquinolines are not desirable, thehydroquinolines separated off in the distillation may be recycled to thesecond stage of the process of the invention.

The quinolines may be used for medicinal purposes; preserving anatomicalspecimens, in the manufacture of the quinolinol sulfates, in themanufacture of niacin, in the manufacture of copper-8-quinolinolates andin the preparation of flavours and perfumes.

The process according to the invention will be further elucidated in thefollowing examples.

EXAMPLE I

A gaseous mixture consisting of 2-(β-cyanoethyl)-cyclohexanone andhydrogen, which was obtained by evaporating liquid2-(β-cyanoethyl)-cyclohexanone and mixing with hydrogen, was passed, for1301 hours, from the top downwards through a vertical tubular reactor of25 mm in diameter and 200 mm in length, which was provided with acatalyst bed and a heating jacket. The catalyst used was palladium onaluminum oxide (0.5% by weight of palladium, bulk density 1.07 grams permilliliter), which was previously treated with hydrogen at 270° C.

The gaseous reaction mixture was subsequently passed through a collectorcooled with ice, in which the reaction product condensed. Afteroperating times of 6, 121, 385, 625, 889, 1153 and 1300 hours, theamount of 2-(β-cyanoethyl)-cyclohexanone passed through and the amountof reaction product obtained were measured for 1 hour under constantconditions. The amount of 2-(β-cyanoethyl)-cyclohexanone was determinedby measuring the loss in weight of liquid2-(β-cyanoethyl)-cyclohexanone. The amount of reaction product obtainedwas determined by changing over from the collector to an empty collectorcooled with ice and measuring the gain in weight. The collected reactionproduct was analyzed gas-chromotographically.

The results are compiled in Table 1.

                                      Table 1                                     __________________________________________________________________________    Operating time, in hours                                                                    6   121 385 625 889 1153                                                                              1300                                    Temp. of gas mixture, in                                                      ° C., measured at 1 mm                                                 over catalyst bed                                                                           200 200 203 207 207 207 207                                     Highest temperature of                                                        catalyst bed, in ° C.                                                                204 203 206 208 211 211 211                                     Space velocity, in grams                                                      of 2-(scyanoethyl)-                                                           cyclohexanone per ml of                                                       catalyst per hour                                                                           0,15                                                                              0,15                                                                              0,15                                                                              0,15                                                                              0,15                                                                              0,15                                                                              0,15                                    Moles of hydrogen per                                                         mole of 2-(3-cyano-                                                           ethyl)-cyclohexanene                                                                        13,2                                                                              13,2                                                                              13,2                                                                              13,2                                                                              13,2                                                                              13,2                                                                              13,2                                    Conversion, in %                                                                            100 100 100 99,2                                                                              97,3                                                                              94,3                                                                              93                                      Yield of quinoline, in %                                                                    1   1   1,5 1,5 2   2   2                                       Yield of decahydro-                                                           quinoline, in %                                                                             49  41  36  35  33  35  32                                      Yield of 5,6,7,8-tera-                                                        hydroquinoline, in %                                                                        41  45  50  50  51  51  51                                      Yield of 1,2,3,4-tera-                                                        hydroquinoline, in %                                                                        6   5,5 6   6   7   7   6                                       Total yield   97  92,5                                                                              93,5                                                                              92,5                                                                              93  95  91                                      __________________________________________________________________________

Part of the resulting reaction mixture was evaporated, mixed withhydrogen and nitrogen, and passed over a catalyst bed consisting ofpalladium on aluminum oxide (0.5% by weight of palladium, bulk density1.07 grams per milliliter) for 1130 hours. The amount of nitrogen was2.56 moles per mole of gaseous reaction mixture and the amount ofhydrogen 7.68 moles per mole of gaseous reaction mixture.

This gaseous starting mixture contained 1.5% by weight of2-(β-cyanoethyl)-cyclohexanone 5.4% by weight of1,2,3,4-tetrahydroquinoline, 1.2% by weight of quinoline, 41.3% byweight of 5,6,7,8-tetrahydroquinoline, 38.5% by weight ofdecahydroquinoline, and 12% by weight of water.

The analyses and measurements were carried out in the same way asdescribed in the first section of this example.

The results are compiled in Table 2.

                                      Table 2                                     __________________________________________________________________________    Operating time, in hours                                                                    25  168 336 504 768 937 1129                                    Temperature of gas mixture                                                    in ° C., measured at 1 mm                                              over catalyst bed                                                                           271 285 285 294 294 304 304                                     Highest temperature of                                                        catalyst bed, in ° C.                                                                266 280 281 290 292 300 301                                     Space velocity of the                                                         gas mixture, in grams                                                         per ml of catalyst per                                                        hour          0,2 0,2 0,2 0,2 0,2 0,2 0,2                                     Conversion, in %                                                                            34,4                                                                              31,3                                                                              31,3                                                                              28,2                                                                              29,7                                                                              28,2                                                                              28,2                                    Yield of quinoline rela-                                                      tive to converted start-                                                      ing mixture, in %                                                                           95  93  93  94  90  94  94                                      __________________________________________________________________________

EXAMPLE II

In the same way as in example 1, a gaseous mixture of2-(β-cyanoethyl)-cyclohexanone and hydrogen, to which also an amount ofnitrogen was added, was passed over a catalyst consisting of palladiumon aluminum oxide (0.5% by weight of palladium, bulk density 1.07 gramsper milliliter) for 1301 hours.

The amounts of hydrogen and nitrogen in the gaseous mixture were 15.6moles and 5.2 moles, respectively, per mole of2-(β-cyanoethyl)-cyclohexanone. The pressure was 1.5 atm.

The results are compiled in Table 3.

After 1301 hours the catalyst was regenerated by treating it with air ata temperature of 200°-300° C. for 20 hours. In the same way as in thefirst section of this example, a gas mixture of2-(β-cyanoethyl)-cyclohexanone, hydrogen and nitrogen was then passedover this catalyst for 722 hours.

The amounts of hydrogen and nitrogen in the gaseous mixture were 15.6moles and 5.2 moles, respectively, per mole of2-(β-cyanoethyl)-cyclohexanone.

The pressure was 1.5 atm.

The results are compiled in Table 4.

    __________________________________________________________________________    Table 3                        Table 4                                        Operating time, in hours                                                                    6   385 889 1300 26  362 721                                    Temperature of gas mix-                                                       ture, in ° C., measured at                                             1 mm over catalyst bed                                                                      200 203 207 207  200 200 205                                    Highest temperature of                                                        catalyst bed, in ° C.                                                                204 206 211 211  204 203 209                                    Space velocity of the                                                         gas mixture, in grams per                                                     ml of catalyst per hour                                                                     0,15                                                                              0,15                                                                              0,15                                                                              0,15 0,15                                                                              0,15                                                                              0,15                                   Conversion, in %                                                                            100 99,9                                                                              97,1                                                                              93,6 100 99,8                                                                              97                                     Yield of quinoline, in %                                                                    0,6 0,7 1,3 1,3  0,8 0,7 1,0                                    Yield of decahydroquino-                                                      line, in %    56  45  38  36   52  43  34                                     Yield of 5,6,7,8-tetra-                                                       hydroquinoline, in %                                                                        36  45  49  45   43  46  49                                     Yield of 1,2,3,4-tetra-                                                       hydroquinoline, in %                                                                        4   5   6   6    4   4   4                                      Total yield   96,6                                                                              95,7                                                                              94,3                                                                              88,3 99,8                                                                              93,7                                                                              88                                     __________________________________________________________________________

Part of the resulting reaction mixture was subjected to fractionaldistillation to remove water. The reaction mixture was then evaporated,mixed with 6.75 moles of hydrogen and 2.25 moles of nitrogen per mole ofgaseous reaction mixture, and passed over a catalyst consisting ofpalladium on aluminum oxide (0.5% by weight of palladium, bulk density1.07 grams per milliliter) for 2402 hours.

The gaseous reaction mixture used as the starting product contained38.1% by weight of decahydroquinoline, 52% by weight of5,6,7,8-tetrahydroquinoline, 5% by weight of1,2,3,4-tetrahydroquinoline, and 3% by weight of quinoline.

The results are compiled in Table 5.

                                      Table 5                                     __________________________________________________________________________    Operating time, in hours                                                                    6   386 725 1322                                                                              1562                                                                              2066                                                                              2401                                    Temperature of gas mix-                                                       ture, in ° C., measured at                                             1 mm over catalyst bed                                                                      264 277 283 293 293 293 293                                     Highest temperature of                                                        catalyst bed, in ° C.                                                                258 275 280 290 290 290 290                                     Space velocity of gas                                                         mixture, in grams per ml                                                      of catalyst per hour                                                                        0,2 0,2 0,2 0,2 0,2 0,2 0,2                                     Conversion, in %                                                                            37,8                                                                              30,4                                                                              32,4                                                                              34,4                                                                              34,2                                                                              32,8                                                                              33                                      Yield of quinoline, rela-                                                     tive to converted start-                                                      ing mixture   94  98  96  99  99  98  98                                      __________________________________________________________________________

Comparative example

In the same way as in example 1, a gaseous mixture of2-(β-cyanoethyl)-cyclohexanone and hydrogen (10 moles of hydrogen permole of 2-(β-cyanoethyl)-cyclohexanone) was passed over a catalystconsisting of palladium on aluminum oxide (0.5% by weight of palladium,bulk density 1.07 grams per milliliter) for 290 hours.

The results are compiled in Table 6, which shows that the conversion andthe yield rapidly decrease.

After 290 hours the catalyst was regenerated by treating it with air ata temperature of 200°-300° C. for 20 hours.

Subsequently, a mixture of 2-(β-cyanoethyl)-cyclohexanone and hydrogen(10 moles of hydrogen per mole of 2-(β-cyanoethyl)-cyclohexanone) wasagain passed over the regenerated catalyst for 71 hours.

The results are compiled in Table 7. It appears from these results thatthe regeneration of the catalyst has only a moderate effect and theconversion and the yield likewise decrease very rapidly.

    ______________________________________                                        Table 6                  Table 7                                              Operating time, in hours                                                                    101    215    289   4    28   70                                Temperature of gas mix-                                                       ture, in ° C., measured at                                             1 mm over catalyst bed                                                                      252    260    272   252  252  252                               Highest temperature of                                                        catalyst bed, in ° C.                                                                --     --     --    --   --   --                                Space velocity of gas                                                         mixture in grams per ml                                                       of catalyst per hour                                                                        0,1    0,1    0,1   0,1  0,1  0,1                               Conversion, in %                                                                            93,5   74     57    100  90   73                                Yield of quinoline, in %                                                                    36     26     21    54   30   20                                Yield of 5,6,7,8-tetra-                                                       hydroquinoline, in %                                                                        33     33     30    24   40   43                                Yield of 1,2,3,4-tetra-                                                       hydroquinoline, in %                                                                        4      2      1     5    4    2                                 Total yield   73     61     52    83   74   65                                ______________________________________                                    

The results set forth in Table 1, represent results undertaken accordingto the process conditions of the first stage of the process of theinvention. It will be noted that conversion proceeds in excellent yieldsfor up to 1300 hours. The total yield of products resulting from theconversion are also excellent.

Table 2 represents results obtained by passing the gaseous startingmixture of the first stage of the process of the invention over adehydrogenation catalyst at temperatures within the ranges of the secondstage of the process in accordance with the invention. It will be notedthat the percent of conversion of products obtained from the first stageof the process in accordance with the invention remains steady for up to1129 hours. It will also be noted that conversion in the second stage ofthe process results in very good yields of quinoline for extendedperiods of time, up to 1129 hours.

Table 3 and Table 4 represent results obtained by employing the samecatalysts, which has been regenerated, for two different consecutiveruns of the first stage of the process. Table 3 represents the resultswith respect to the percent conversion and total yield products producedin accordance with the first stage of the process of the invention. InTable 3, the dehydrogenating catalyst was effective for up to 1300hours. The results of Table 4 are based on regenerating the catalystused in Table 3 and then using that catalyst again with fresh2-(beta-cyanoethyl)-cyclohexanone to undertake the first stage of thereaction process with the same catalyst. The results of Table 4 indicatethat percent conversion and total yields will remain constant, even onreuse of the catalyst.

Table 5 represents results concerning the second stage of the process ofthe invention. Reaction products obtained from the first stage of theprocess of the invention, as in Table 3 and in Table 4. These resultsare comparable to those set forth in Table 2 (an experiment dealing withthe second stage of the process of the invention). As can be noted,conversion and percent yields of quinoline remain constant up to 2400hours.

Table 6 and Table 7 represent results when a process of treating2-(beta-cyanoethyl)-cyclohexanone with a dehydrogenation catalyst atprior art temperatures. As will be noted in Table 6, percent conversionand total yield decrease with time.

Table 7 represents results obtained by reducing the catalyst employed inthe experiments set forth in Table 6 after the catalyst has beenregenerated. The experiments in Table 7 were undertaken at temperaturesoutside the scope of the invention claimed. The results of Table 7 areconsistent with the results of Table 6, in that undertaking thedehydrogenation of 2-(beta-cyanoethyl)-cyclohexanone in one step, athigh temperatures, results in percent conversion and total yielddecreases with time. Such results reflect deactivation of the catalystused.

What is claimed is:
 1. In a process for preparing quinolines, bycontacting a vaporized compound of the formula ##STR2## wherein each R₁,R₂, R₃ and R₄ is the same or different and is hydrogen or alkyl groupsof 1 to 4 carbon atoms, and wherein the summation of the carbon atoms ofR₁, R₂, R₃ and R₄ is no greater than 10, with a dehydrogenation catalystin the presence of hydrogen, the improvement consisting essentially ofconducting said process in 2 stages by the steps of:introducing saidvaporized compound into a first stage wherein said compound is contactedwith a dehydrogenation catalyst at a temperature of 185 to 220 degreesC., and removing therefrom a gaseous mixture containing vaporizedreaction products thus formed; introducing a vaporized mixturecontaining said reaction products into a second stage wherein saidreaction products are contacted with a dehydrogenation catalyst in thepresence of hydrogen at a temperature of between 260 and 300 degrees C.2. The process of claim 1 wherein said gaseous mixture containingvaporized reaction products is directly introduced into said secondstage as said vaporized mixture.
 3. In a process for preparingquinoline, by contacting 2-(beta-cyanoethyl)-cyclohexanone in thevaporized state at elevated temperatures with a dehydrogenation catalystin the presence of hydrogen, the improvement consisting essentially ofconducting said process in 2 stages by the steps of:introducing saidvaporized 2-(beta-cyanoethyl)-cyclohexanone into a first stage whereinsaid 2-(beta-cyanoethyl)-cyclohexanone is contacted with adehydrogenation catalyst at a temperature of 185 to 220 degrees C., andremoving therefrom a gaseous mixture containing vaporized reactionproducts thus formed; introducing a vaporized mixture containing saidreaction products into a second stage wherein said reaction products arecontacted with a dehydrogenation catalyst in the presence of hydrogen ata temperature of between 260 and 300 degrees C.
 4. The process of claim3 wherein said gaseous mixture containing vaporized reaction products isdirectly introduced into said second stage as said vaporized mixture.